tbuckley/cabot-search huggingface dataset:
Risk factors for early relapse in patients with biliary tract cancers who underwent curative resection: An exploratory subgroup analysis of JCOG1202.
Authors: Hiroaki Yanagimoto, Kohei Nakachi, Masafumi Ikeda, Masaru Konishi, Gakuto Ogawa, Yusuke Sano, Tatsuya Nomura, Hiroo Yanagibashi, Kazuto Shibuya, Hirofumi Shirakawa, Amane Takahashi, Yoshihiro Sakamoto, Isamu Makino, Etsuro Hatano, Naoto Gotohda, Masato Ozaka, Takeshi Terashima, Takuji Okusaka, Junji Furuse, Makoto Ueno
Journal: Journal of Clinical Oncology (2023)

541 Background: Relapse after highly invasive surgery for biliary tract cancers (BTCs), especially in the early postoperative period, causes medical, psychological, social, and economic disadvantages to the patients. However, approximately 30% of patients with curatively resected BTCs experience relapse within the first 12 months. JCOG1202 (UMIN000011688) is a randomized phase III trial conducted in patients with resected BTCs showing the benefit of adjuvant S-1 for overall survival. This study aimed to investigate the risk factors for early relapse of resected BTCs in the JCOG1202 cohort. Methods: Of the 440 patients enrolled in the JCOG1202, 217 patients who received surgery alone (arm A) and 207 patients who received adjuvant S-1 (arm B) were eligible and included in this analysis. Early relapse was defined as relapse or death within 12 months after enrollment. Predictive factors for early relapse were assessed using logistic regression analyses. Results: Postoperative early relapse was observed in 59 (27.2%) and 38 (18.4%) of patients in arm A and arm B, respectively. In multivariable logistic regression analysis for the 424 eligible patients, postoperative CA19-9 levels &gt;37 u/ml (odds ratio (OR): 2.790, 95% confidence interval (CI): 1.262-6.170), poorly differentiation (vs. well-differentiated/papillary) (OR: 4.746, 95% CI:1.927-11.688), moderate differentiation (vs. well-differentiated/papillary) (OR: 1.955, 95% CI:1.071-3.567), lymph node metastases &gt; 4 (vs. 0) (OR: 3.991, 95% CI: 1.674-9.514), lymph node metastases 1-3 (vs. 0) (OR: 2.661, 95% CI: 1.471-4.814), and presence of residual tumor (OR: 2.171, 95% CI: 1.070-4.408) were independent risk factors for early relapse. Importantly, adjuvant S-1 chemotherapy significantly reduced early relapse (OR: 0.491, 95% CI: 0.290-0.833). Similar results were observed in arm B. Conclusions: Postoperative CA19-9 level, tumor differentiation, lymph node metastases, and the residual tumor significantly impact early relapse in patients with curatively resected BTCs. Although adjuvant S-1 chemotherapy was effective in reducing early relapse, similar factors tended to be the risk factors in patients receiving adjuvant S-1 chemotherapy. Patients at high risk of early relapse may need more intensive perioperative therapy. Clinical trial information: UMIN000011688 .
Comparative study of prognosis of conversion therapy vs palliative therapy without surgery in colorectal cancer with synchronous liver metastasis according to risk classifications.
Authors: Hiroaki Nozawa, Tatsuya Tsushima, Nobumi Suzuki, Mitsuhiro Fujishiro, Yoshikuni Kawaguchi, Kiyoshi Hasegawa, Soichiro Ishihara
Journal: Journal of Clinical Oncology (2023)

107 Background: Recent progress in chemotherapy and targeting antibodies has brought an increased opportunity of conversion to curative resection in initially unresectable/metastatic colorectal cancer (CRC). Survival of CRC patients with liver metastasis who underwent conversion therapy was reported better than that of those who received palliative systemic therapy without surgery. However, it is largely unknown whether such patients who undergo conversion therapy can uniformly benefit from the surgical resections. Methods: We retrospectively reviewed 172 patients who received systemic therapy for unresectable CRC with synchronous liver metastasis in our hospital between 2010 and 2020. Patients were divided into ‘Conversion’ group (n = 45) and ‘Non-conversion’ group (n = 127) according to conversion to surgical resection with curative intent. Patients were also divided by pre-treatment Fong’s Clinical Risk Score (CRS), in addition to Grade A, B, or C group according to Japanese Grade Classification for colorectal liver metastasis. Overall survivals (OS) of Conversion and Palliation groups were compared according to these risk classifications. Results: Overall, 3-year OS rate was 76% for Conversion group and 25% for Non-conversion group (p &lt; 0.001). Three-year OS rate for patients in Conversion group with CRS 1-3 was 73%, whereas that for those with CRS 4-5 was 77%. Both were higher than the rates for the counterparts in Non-conversion group (26% and 24%, respectively; both p &lt; 0.001). When confined to Grade A and B of Japanese Grade Classification, 3-year OS rate was 68% for Conversion group and 25% for Non-conversion group (p = 0.002). The 3-year OS rate for the patient groups was 83% and 25% respectively in the analyses of patients classified into Grade C (p &lt; 0.001). Conclusions: Conversion therapy provided a significant survival benefit in CRC patients with liver metastasis regardless of risk groups by the above classifications. Both classifications did not discriminate OS curves well between Conversion and Non-conversion groups in the era of conversion therapy.
Association of awareness and use of patient navigation services for colorectal cancer screening with test completion and likelihood of future use.
Authors: Shama Alam, Xuan Zhu, Linda Squiers, Leah Helmueller, Gabriel Madson, Brian Southwell, Carlye Gates, Bonny Kneedler, Paul J. Limburg, Lila J Finney Rutten
Journal: Journal of Clinical Oncology (2023)

61 Background: Although several guideline-recommended colorectal cancer (CRC) screening modalities have been shown to reduce CRC incidence and mortality, adherence remains below U.S. public health goals. Patient navigation services have been shown to improve CRC screening completion. Patient navigation services, including outbound phone, text, and e-mail reminders, and inbound phone support (&gt;200 languages) are included with all mt-sDNA test (Cologuard) orders. A website and financial assistance (upon request and qualification) are also available for patients. We developed a survey, informed by behavioral theory, to identify psychosocial and communication factors associated with completion of mt-sDNA screening including questions to evaluate awareness and use of navigation services. Methods: Adults aged 45-75 years, with a US postal address, who received a valid order for mt-sDNA screening between 5/21-9/21 were eligible for sampling. RTI administered the survey between 3/22-6/22. Participants had the option to complete electronic- or paper-based surveys. We conducted crosstabulation with Chi Square to assess whether awareness and use of navigation services was significantly associated with (a) test completion within 6 months of the order date and (b) likelihood of future mt-sDNA use. Results: 2,973 participants completed the survey (RR= 21.7%; 65.15% by web and 34.85% by paper). Responders and non-responders did not differ significantly by age or sex. For each navigation service, awareness was significantly higher among those who completed the mt-sDNA test compared to those did not. Across all services, awareness was significantly higher among respondents reporting they were ‘very likely’ to complete mt-sDNA if recommended by a healthcare provider in the future than all other responses combined. A significantly higher proportion of completers (vs. non-completers) reported receiving the email reminder, using the Cologuard website, and using the English language inbound phone support. A significantly higher proportion of those “very likely” to complete mt-sDNA screening in the future reported receiving the email reminder, using the Cologuard website, and using the English language inbound phone support. Conclusions: Awareness and use of patient navigation services was associated with higher completion of the mt-sDNA test and with greater likelihood of future mt-sDNA test use. Patient navigation services comprised of evidence-based strategies, such as reminders, support patient adherence to CRC screening.
Multifocal early gastric neoplasms of three or more lesions versus single lesion without recurrence: A comparative study.
Authors: Gyu Young Pih, Ji Hoon Yoon
Journal: Journal of Clinical Oncology (2023)

329 Background: As indication for endoscopic resection for gastric neoplasms have been expanded, patients receiving multiple times of endoscopic resection for metachronous or synchronous lesions have been increasing. We aimed to compare clinicopathologic characteristics of patient with gastric neoplasm in a single location and multifocal lesions of three or more. Methods: From January 2006 to December 2021, 255 patients underwent endoscopic resection for three or more of multifocal lesions at tertiary medical institution were reviewed retrospectively and 8667 patient showed no recurrence after endoscopic resection for single lesion. The clinicopathologic characteristics of index gastric lesions were compared. Results: The male ratio was higher in multifocal lesions group than single lesion group (83.9% vs. 68.4%, P &lt; 0.001). Diabetes mellitus was significantly more in multifocal lesions group than single lesion group (20.4% vs. 18.4%, P = 0.046), however hypertension, cardiovascular disease, kidney disease, and hepatitis showed no significant difference between the two groups. Smoking rate was significantly higher in the multifocal lesions group (current smoker 31.0% vs. 25.4%, and ex-smoker 24.7% vs. 24.8%, P = 0.028). In rapid urease test for Helicobacter pylori infection, the multifocal group showed significantly higher positives (54.9% vs. 40.8%, P &lt; 0.001). Tumor depth, lymphovascular invasion, and perineural invasion showed no significant differences. Conclusions: Patients with multifocal early gastric neoplasms showed higher male ratio, higher rate of diabetes mellitus, and smoking rate compared with single lesion group. In addition, Helicobacter pylori infection was also significantly higher in patients with multifocal gastric neoplasm.
Comprehensive molecular profiling in patients with advanced biliary tract cancers (BTC) in a Latinx-rich cohort.
Authors: Vidit Kapoor, Sylvia Keiser, Qianqian Liu, Joel Michalek, Sukeshi Patel Arora
Journal: Journal of Clinical Oncology (2023)

605 Background: BTC are genetically diverse and heterogeneous. Despite knowledge of molecular subtypes of BTC, the distribution of molecular aberrations in the Latinx population has been understudied. These may have prognostic and/or predictive implications. Therefore, we analyzed our cohort of Latinx-rich patients with advanced BTC. Methods: We analyzed patients with advanced BTC, who were seen at the Mays Cancer Center from Jan 2018-Dec 2021. Tumor samples profiled by Next Generation Sequencing (NGS) were identified retrospectively. Associations between demographics, clinical characteristics, and genetic alterations were identified. Results: 88 patients with locally advanced/metastatic BTC were identified. 50 (56.2%) were Latinx. 42 (47.7%) had intrahepatic CA (IHCA), 14 (15.9%) had extrahepatic CA (EHCA), 16 (18.2%) had Gall Bladder Carcinoma (GBC) and 16 (18.2%) had Ampullary/Periampullary Carcinoma (APC). 49 (56%) had NGS on their tumors out of which 30 (61.2%) were Latinx and 19 (38.8%) were non-Latinx. The most commonly altered genes were TP53 (34.7%), KRAS (24.5%), ARID1A (16.3%), BRCA-2 (12.2%), PDL-1 (12.2%), FGFR (12.2%), MET (10.2%), PTEN (10.2%) and HER-2 (8.2%). 14.3% patients had no identifiable mutations. There was no significant difference observed in the rates of different molecular mutations between Latinx and non-Latinx (p=1) and among different histologies of IHCA, EHCA, GBC and APC (p=1). The Median Overall Survival (OS) for Latinx population was 16.1 months (95% CI 12.3-28.2) which was similar to the median OS for non-Latinx population of 15.5 months (95% CI 11.6-28.6) (p=0.69). The median OS was not different due to the presence or absence of any one mutation (p values ranged from 0.04 to 0.9). Conclusions: BTCs are genetically diverse. Somatic alterations were identified in 85% patients who were tested. Only 56 % had molecular testing, when it should be 100% in advanced BTC, per NCCN guidelines. This may be due to inadequate tissue, lack of funding, use of alternate ctDNA, or the patient may have died before getting to testing/repeat biopsy. The likelihood of having a genetic alteration was similar between Latinx and non-Latinx patients and among different sites of disease. Latinx and Non Latinx with advanced BTC had similar survival rates. Survival rate was not different due to the presence or absence of any one mutation. Future studies should prospectively investigate implementation programs for NGS in tumor and blood in all patients with BTCs.
Long-term outcomes after laparoscopy-assisted total or proximal gastrectomy with nodal dissection for clinical stage I gastric cancer: Japan Clinical Oncology Group study (JCOG1401).
Authors: Shinichi Sakuramoto, Hitoshi Katai, Hiroshi Katayama, Shintaro Iwamoto, Yasuhiro Hasegawa, Takashi Nomura, Shigeto Makino, Masaya Watanabe, Takeshi Omori, Takaki Yoshikawa, Toshiyasu Ojima, Masanori Terashima
Journal: Journal of Clinical Oncology (2023)

305 Background: JCOG0912 supports the non-inferiority of laparoscopy-assisted distal gastrectomy (LADG) compared with open distal gastrectomy (ODG) for clinical stage I gastric cancer relapse-free survival (RFS), suggesting that LADG should be considered a standard treatment option when performed by experienced surgeons. No prospective study evaluating laparoscopy-assisted total gastrectomy (LATG) and laparoscopy-assisted proximal gastrectomy (LAPG) has been completed in terms of both safety and long-term survival. Considering that the results of the phase III trial to evaluate the long-term outcome of LADG (JCOG0912) could guarantee that of LATG/LAPG, we conducted a single-arm confirmatory trial (JCOG1401) to evaluate the safety of LATG/LAPG for clinical stage I proximal gastric cancer and JCOG1401 confirmed the safety of LATG/LAPG. Long-term outcomes as the secondary endpoints of this study are reported here after 5-year follow-up period. Methods: Laparoscopic operators were limited to credentialed surgeons. The extent of nodal dissection was selected based on the Gastric Cancer Treatment Guidelines in Japan. The primary endpoint was the proportion of grade 2 (CTCAE ver. 4.0) or greater esophageal anastomotic leak. The sample size was determined to be 245 considering a threshold of 8% and expected value of 3% with a one-sided alpha error of 2.5% and statistical power of 90%. The secondary endpoints were overall survival (OS) and RFS. Results: Between April 2015 and February 2017, 245 patients were enrolled. Among them, 1 patient was excluded from safety analysis due to ineligible. LATG/LAPG was performed in 195/49. 170/47/17/8/2 patients had pStage IA/IB/II/IIIA/IIIB disease and 190/31/15/8 patients had pT1/T2/T3/T4 disease, respectively. Grade 2 or greater esophageal anastomotic leak was 2.5% (6/244) (95% CI 0.9-5.3), as previously reported. 5-year OS was 91.2% (95% CI 86.9-94.2). 5-year RFS was 90.0% (95% CI 85.5-93.2). Among 22 deaths, 14 patients died without recurrence and 8 patients died with recurrence. Twelve recurrences were observed in 5/2/4/1 patients for pT1/T2/T3/T4. The sites of recurrence were peritoneal metastasis in 2 cases, hematogenous metastasis in 9 cases (liver: 6, bone: 2, lung: 1), and other in 1 case. Conclusions: The long-term outcomes of LATG/LAPG for Stage I gastric cancer patients were excellent and seem comparable to those of open procedures. Similar to JCOG0912, JCOG1401 guarantee the long-term survival of LATG/LAPG. Clinical trial information: UMIN000017155 .
Treatment selection and outcomes of locally advanced esophageal cancer in octo- and nonagenarians: Is a curative intent multimodal approach feasible?
Authors: Nabeel Ahmed, James Tankel, Jamil Asselah, Thierry Alcindor, Joanne Alfieri, Marc David, Sara Najmeh, Jonathan Cools-Lartigue, Jonathan Spicer, Carmen L. Mueller, Lorenzo Ferri
Journal: Journal of Clinical Oncology (2023)

333 Background: Neoadjuvant therapy followed by en bloc surgical resection affords the highest rates of survival from locally advanced esophageal cancer (LAEC) and represents the standard of care. However, patients of advanced age may not be offered this approach due to concerns over toxicity/tolerability. The outcomes of different treatment modalities for patients aged 80 and above with LAEC are not well described. Methods: A retrospective, single center, cohort analysis was performed on a prospectively maintained comprehensive esophageal cancer database. Between 2010-20, all patients ≥80yrs with locally advanced esophageal/GEJ cancer (cT2-4a, Nany, M0) were identified and outcomes stratified according to the following treatment categories: Neoadjuvant chemotherapy (nCT) or chemoradiotherapy (nCRT) followed by surgery; definitive CRT (dCRT); upfront surgery; palliative CT or RT; or best supportive care (BSC). Data presented as median(range). Univariate analysis used for clinicopathological data (*p&lt;0.05). Survival was compared with log rank analysis (Mantel Cox). Results: 79 patients ≥80 yrs with LAEC were identified. Median age was 83yr (80-97) and Charlson comorbidity index=7 (6-10). Most were cT3 (73%), cN- (56%) and adenocarcinoma (62%). Treatment approaches included: neoadjuvant (nCT(n=11)/nCRT(N=5)) + surgery (16/79(20%)); surgery alone (19/79 (24%)); dCRT (12/29(15%)); palliative RT or CT (24 + 3/79(34%)); BSC (5/79(6%)). Neoadjuvant consisted of nCT (FLOT=4; carbo-taxol =4; FOLFOX=2; CP+pembro=1) and nCRT (CROSS=5) and most received the intended full treatment/cycles (10/16:63%). Surgery was performed in 35 (age=82(80-96)), with major complications (grade 3-5) in 13/35 (37%) and 90-day mortality in 3/35(8.5%). Overall Survival for the entire cohort was 58% (1yr) and 19% (3yr), but highest with nCT/nCRT+surgery (94%/46%)*, followed by surgery alone (68%/39%), dCRT (58%/8%), palliative treatment (40%/4%), and BSC (0%/0%). Curative intent treatment (nCT/nCRT/surgery/dCRT) had significantly increased 1 and 3-yr survival compare to palliative treatment (76%/31% vs 34%/3.3%)*. Conclusions: Multimodal standard of care treatment, including surgical resection, of locally advanced esophageal cancer in octo/nonagenarians is feasible and safe in a subset of this high-risk population and associated with improved outcomes compared to other approaches. Age alone should not bias against curative-intent treatment in elderly patients with esophageal cancer.
Three-dimensional radiotherapy dose prediction in patients with liver and pancreas cancer treated with the Viewray system.
Authors: Dong-Yun Kim, Bum-Sup Jang, Eunji Kim, Jae Sik Kim, Eui Kyu Chie
Journal: Journal of Clinical Oncology (2023)

612 Background: The radiotherapy (RT) planning process for patients with gastrointestinal tract cancers is regarded as a time-consuming and complicated task due to proximity of multiple organs at risk (OARs). Dose prediction model based on deep learning might be a solution to increase efficiency by reducing the time required to find the optimal plan. Dose distribution model was developed using a three-dimensional (3D) U-Net deep learning. Methods: Altogether RT plan of patients with liver cancer (N=40) and pancreatic cancer (N=26) were acquired from the MRIdian (Viewray Technologies, Oakwood Village, OH) treatment planning system from 2016 to 2018. Magnetic resonance (MR) images for RT, planning dose, and contoured RT structures were retrospectively collected. The 3D U-Net was employed, and transfer-learning was performed on the training set (N=60, 91.3%). The initial learning rate was 0.1, decreasing by 10% every 5 epochs, for a total of 200 epochs. A developed model was evaluated by the testing set (N=5, 7.7%). The difference between ground truth and predicted dose was compared by calculating normalized minimum, maximum, and mean doses of the planning target volume (PTV) and OARs. Results: Root-mean-square error (RMSE) of voxels between ground truth and predictive dose was 3.04 (range 2.29-3.79). Percentage of mean dose difference and standard deviation between clinical and prediction models were 1.75 ± 2.84%, 0.08 ± 0.11%, 0.13 ± 0.08%, 0.05 ± 0.03%, 0.07 ± 0.05% for PTV, duodenum, liver, kidney, and stomach, respectively. And the percentage of max dose difference between the two were 0.91 ± 0.01%, 0.34 ± 0.43%, 0.63 ± 0.39%, 0.25 ± 0.18%, 0.33 ± 0.30%, respectively. Overall, the predicted normalized target DVH metrics were within 2% of the ground truth plans. Conclusions: We developed a deep learning model for dose prediction in liver and pancreatic cancer using MR images acquired from MRIdian system. Larger-scale training and validation are required to prove the efficacy of the dose prediction model by the 3D U-Net.
Efficacy and safety of neoadjuvant immune checkpoint inhibitors in patients with localized mismatch repair deficient colorectal cancer: A systematic review.
Authors: Udhayvir Singh Grewal, Kruti Bhagirath Vora, Aparna Raj Parikh, Amit Mahipal, Sakti Chakrabarti
Journal: Journal of Clinical Oncology (2023)

149 Background: Clinical data demonstrating remarkable anti-tumor activity of immune checkpoint inhibitors (ICI) in patients with mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) and preclinical data suggesting enhanced efficacy of ICIs in the neoadjuvant setting than in the adjuvant setting led to numerous studies with neoadjuvant ICI in various tumor types including in dMMR CRC. We performed a systematic literature review of the published studies reporting the efficacy and safety of neoadjuvant ICIs in patients with localized dMMR CRC. Methods: Medline and Embase were searched for eligible case reports, case series, and clinical trial reports. Eligibility criteria included: 1. patients aged 18 years or older, 2. localized dMMR CRC, and 3. received neoadjuvant therapy primarily with ICI. Patients receiving radiation or chemotherapy along with ICI were excluded. The systematic review was conducted according to the PRISMA harms guidelines. Results: The database search yielded 143 citations which were reviewed by 3 authors (UG, KV, and SC), and 14 citations fulfilled all criteria for inclusion. The analysis included 173 patients with colon cancer (CC) and 19 with rectal cancer (RC). Among the patients with CC, 41 (24 %) received single-agent programmed death 1 (PD-1) blocker, and 132 (76 %) received dual blockade with an anti-PD-1 agent plus an anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) agent. Resection was performed in 171/173 (99%) patients, and 117/171 (69%) achieved complete pathological response (pCR). After median follow-up ranging between 8 and 15 months, none of the patients experienced cancer relapse. Among patients with RC, 16/19 (84%) received a PD-1 blocker, and 3 (16%) received dual PD-1 plus CTLA-4 blocker. Complete clinical response (cCR) was reported in 14/19 (74%) patients, and of the 5 patients who underwent surgery, 4 (80%) achieved pCR. All patients remained progression-free after median follow-up ranging from 6 to 12 months. Cancer progression or death on neoadjuvant ICI was not reported in any studies with CC or RC patients, and only two studies reported grade 3+ toxicity in 3% of CC patients. Conclusions: Neoadjuvant therapy with ICIs results in a remarkably high rate of clinical and pathological tumor regression with negligible safety concerns in patients with dMMR localized CRC. Well-designed clinical trials with long-term follow-up are needed to evaluate the organ-sparing potential of neoadjuvant ICI therapy in patients with dMMR CRC.